Controlled Environments, July/August 2015

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W W W. C E M A G . U S

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Modular cleanrooms: An evolving industry ISO 14644 and biopharma monitoring Cleanrooms have a dirty little secret

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TABLE OF CONTENTS

July/August 2015 • www.cemag.us

Controlled Environments

TM

July/August 2015 Vol. 18 • No. 5

14 Cleanroom Design and Environmental

Control Technologies

7

A look at the RFAB semiconductor facility of Texas Instruments.

Texas Instruments’ Richardson Fabrication Facility (RFAB). Credit for this image and cover image: Texas Instruments

7

The Implications of ISO/DIS 14644-1.2 How does this standard affect biopharma monitoring of clean areas?

10

Modular Cleanroom Systems: An Evolving Industry

12

The Cleanroom’s Dirty Little Secret

12

A discussion of the four main styles of modular cleanrooms.

Protection is a two-way street.

16

Personalized Medicine, Companion Diagnostics, and NGS Diagnostic Tests Personalized medicine has the potential to be the biggest advance in health in many decades.

18 20 22

Particles Cling to der Waals Geckos’ feet have something in common with particles and soils — force.

Benches and Enclosures Product Showcase Cleanroom Training How to resource training for your cleanroom personnel.

20 DEPARTMENTS 6 From the Editor 24 How It Works

25 Trending on the Web 26 Cleanroom Tip and Index

18

Everything you need in one clean package... ™

Find current information on everything from pure materials through protective packaging, from state-of-the-art facility construction through day-to-day cleaning, and control challenges affecting quality and yield.

www.cemag.us

6 FROM THE EDITOR

July/August 2015

• www.cemag.us

Controlled Environments

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STEM Education is Vital

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he blogs section of the Controlled Environments website gives me a chance to write in-depth about timely topics, and to attach my personal voice to the subject matter at hand. A topic that’s become quite close to my heart recently has been STEM (science, technology, engineering, and mathematics) education.

Back in May, I wrote about members of the CBS sitcom The Big Bang Theory sponsoring a STEM scholarship fund at UCLA. MaryBeth DiDonna Editor The school holds a special place in the hearts of many who work with the show … actress Mayim Bialik, who plays the quirky neuroscientist Amy Farrah Fowler, earned both her bachelor’s degree and her doctorate in neuroscience from UCLA. The show also employs a UCLA physics and astronomy professor as its science consultant.

Caltech — home of NASA’s Jet Propulsion Laboratory, in whose cleanroom the Mars rover Curiosity was created — is another educational institution represented on the show, as many of the main characters are employed there as researchers. One episode even featured three of the characters working in a cleanroom, and hijinks ensued when a bird somehow found its way inside.

Another blog entry came about after Nobel laureate Tim Hunt made public remarks about working with women in the laboratory. “Three things happen when [girls] are in the lab: you fall in love with them, they fall in love with you, and when you criticize them they cry,” he told an audience gathered at the World Conference of Science Journalists in Korea. Hunt was quickly taken to task by social media, and offered a halfhearted apology via BBC 4 Radio. He later resigned his position with University College London, but in a joint newspaper interview with his wife (herself a University College London professor) the couple said that he had been unfairly targeted for his “joking” remarks.

I admit that it was a bit discouraging gathering sources for that blog entry — I searched for other examples of discrimination against women in STEM fields, and there was certainly no shortage. I picked a few to highlight, such as an article penned by a woman who was faced with crude remarks upon her admission to the prestigious Massachusetts Institute of Technology. Another photo, which was widely circulated around Twitter, showed a Target toy aisle that differentiated between “building sets” and “girls’ building sets.”

Speaking of Twitter … within a couple days of the Tim Hunt controversy, a retaliation of sorts sprang up on the social media platform. A feminist web magazine urged women scientists to tweet photos of themselves at work, using the hashtag #distractinglysexy in a tongue-in-cheek manner. The response was overwhelming. Women from all sorts of STEM-related fields — lab technicians, doctors and nurses, archaeologists, marine biologists, and many more — used the hashtag to draw attention to their work and the inequalities they face. Also included in this movement were women who work in cleanrooms, and several of them graciously spoke with me about what they do in the clean lab, as well as their thoughts on STEM education.

I’m grateful for the blog feature on our website because it enables me to address things as they happen (and track the response from our readership in real time), rather than have to wait a few weeks for our print edition — as we all know, in our instant access society, even waiting a day or two can be too late. Visit cemag.us/blogs for more.

Vol. 18 • No. 5 David A. Madonia, General Manager david.madonia@advantagemedia.com • 973-920-7048 Bea Riemschneider, Editorial Director bea.riemschneider@advantagemedia.com MaryBeth DiDonna, Editor marybeth.didonna@advantagemedia.com Editorial Advisory Board Charles W. Berndt, C.W. Berndt Associates Ltd. Adam Giandomenico, Particles Plus Inc. Scott Mackler, Cleanroom Consulting LLC Gregg A. Mosley, Biotest Laboratories Inc. Robert Nightingale, Cleanroom Garments Bipin Parekh, Ph.D., Entegris Inc. Michael Rataj, Aramark Cleanroom Services Howard Siegerman, Ph.D., Siegerman and Associates LLC Scott Sutton, Ph.D., Microbiology Network Inc. Art Vellutato, Jr., Veltek Associates Inc. Bob Vermillion, CPP/Fellow, RMV Technology Group LLC ADVERTISING/SALES NEW ENGLAND Luann Kulbashian 973-920-7685 luann.kulbashian@advantagemedia.com MID-ATLANTIC Joy DeStories 973-920-7112 joy.destories@advantagemedia.com MID-ATLANTIC Traci Marotta 973-920-7182 traci.marotta@advantagemedia.com MID-ATLANTIC Greg Renaud 973-920-7189 greg.renaud@advantagemedia.com MIDWEST Tim Kasperovich 973-920-7192 tim.kasperovich@advantagemedia.com MIDWEST Jolly Patel 973-920-7743 jolly.patel@advantagemedia.com WEST Fred Ghilino 973-920-7163 fred.ghilino@advantagemedia.com

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FACILITY MONITORING

July/August 2015 • www.cemag.us

7

The Implications of ISO/DIS 14644-1.2 How does this standard affect biopharma monitoring of clean areas? he International Standards Organization (ISO) has published a Draft International Standard (DIS) for clean areas. Quality control managers in the pharmaceutical and biotechnology industries are curious about how this will impact their monitoring and compliance requirements.

Of foremost concern in the life science industry is the apparent removal of the > 5 μm particle concentration in ISO Class 5 clean areas when compared to the 1999 version. In the 1999 ver-

Jim Strachan, MBA Randy Grater Climet Instruments

T

Staphylococcus aureus

sion, the limit is 29 particles per cubic meter. This change to the ISO/DIS 14644 standard is a major concern for a number of reviewers.

The reasons for the de-emphasis on the 5 μm ISO Class 5 limit include: Sampling and statistical limitations for particles in low concentrations make classification inappropriate; and Sample collection limitations for both particles in low concentrations and sizes greater than 1 μm make classification at this particle size inappropriate, due to potential particle losses in the sampling system.

According to Farquharson (2012), “Once the

bacteria cluster > 5 μm. Credit: Centers for Disease Control and Prevention

DIS standard is ratified, and assuming the concentration limit for the 5 μm column for ISO Class 5 is blank, then without further clarification this particle size cannot be used for classification in accordance with the ISO 14644-1.” He continues, “However, monitoring may be a different matter.”

In the life science industry, this change presents a unique dilemma on how to support regulatory requirements set out in the European Union Good Manufacturing Practice (EU GMP) Annex 1. It is even more sensitive due to the replication of the EU GMP Annex 1 requirements in the Pharmaceutical Inspection Co-operation Scheme (PIC/S) GMP Annex 1 No. 4, the World Health Organization (WHO) GMP for sterile pharmaceutical products Annex 6 No. 4.6.1, and the Chinese GMP regulations.

We know that in 2011 to 2012, experts were working on wording to be included in the standard that would allow the pharmaceutical industry regulatory authorities to provide their own guidance outside the boundaries of the standard.

Regardless, the ISO/DIS 14644-1.2 has a third footnote that is often lost in the minutiae, and many erroneously presume that monitoring of the > 5 μm particle is no longer required. The DIS standard states (in footnote f): “In order to undertake classification at this particle size, use of the macro-particle descriptor M should be considered for > 5 μm.”

The above references ISO/DIS 14644-1, Annex C, entitled “Counting and sizing of airborne macroparticles.” Per ISO/DIS 14644-1.2 section C.1: “In some situations, typically those related to specific process requirements, alternative levels of air cleanliness may be specified on the basis of particle populations that are not within the size range applicable to classification.”

ISO14644-1 pertains to classification of cleanrooms. Contrary to some claims, Annex C was strengthened in revision 1.2 of the draft standard, which was released in 2014. This new version of the ISO 14644-1.2 does not eliminate the 5 μm classification where there are specific process requirements. These are generally found in phar-

8 maceutical, biotechnology, and life sciences.

Quality control personnel need to know why they are monitoring certain particle sizes. This is of paramount importance in the life science industry whose products affect public safety and therefore company reputations and business continuity. No doubt, environmental monitoring of clean areas in the life science industry is a mission critical application, and the one single activity that has the most impact on quality control.

The reason we monitor > 5 μm particles in the biopharma industry is twofold. First, to provide an early warning that a potential problem may be occurring. Indeed, most ISO Class 5 clean zones have counts of zero or one on the > 5 μm channel.

Moreover, viable microorganisms whose individual sizes are generally less than 1 μm tend to form in pairs, chains, and clusters. These colony forming units together often have a size greater than 5 μm. Therefore, a laser scattering aerosol particle counter (LSAPC) is metaphorically the Table 1: EU GMP:2008,

However, consecutive or regular counts due to low levels are an indicator of a possible contamination event and should be investigated.”

This clause in the EU GMP is supported in the new draft ISO/DIS 14644-1.2 standard, Annex C, section C.2.1, which states: “If contamination risks caused by particles larger than 5 μm are to be assessed, sampling devices and measurement procedures appropriate to the specific characteristics of such particles should be employed.

The measurement of airborne particle concentrations with size distributions having a threshold size between 5 μm and 20 μm can be made in any of two defined occupancy states; at-rest and operational.” (Emphasis added.)

Given the EU GMP provides a table for particle counts in clean zones “at rest” and “in operation” (see Table 1), the statement above shows that ISO/ DIS 14644-1.2 draft standard is in harmony with EU GMP Annex 1.

Maximum permitted number of particles per m3 equal to or greater than the tabulated size

Annex 1, No. 4 and 5

EC GMP

ISO

At rest

Grade

Class

0.5 μm

5.0 μm

0.5 μm

5.0 μm

A

4.8

3,520

20

3,520

20

B

5

3,520

29

352,000

2,900

C

7

352,000

2,900

3,520,000

29,000

D

8

3,520,000

29,000

not defined

not defined

canary in a coal mine, because it provides an early warning of a potential problem.

This is confirmed in the EU GMP Annex 1, No. 13, which again provides the most common sense approach to monitoring in the Life Science industry: “In Grade A [ISO Class 4.8] and B [ISO Class 5] zones, the monitoring of the > 5 μm particle concentration count takes on particular significance as it is an important diagnostic tool for early detection of failure. The occasional indication of > 5 μm particle counts may be false counts due to electronics noise, stray light, coincidence, etc.

In operation

Additionally, 14644-1.2 section C.2.2 includes an example of how to describe a measurement of a particle count of 29 particles > 5.0 μm using a particle counter. This size limit of 29 particles > 5.0 μm is the current standard for an ISO Class 5 clean area, according to ISO 14644-1.

Therefore, contrary to what others may be suggesting, the > 5 μm particle size should continue to be an important element of risk assessment and monitoring in the life science industry.

Monitoring is about control. When we understand why we are monitoring, then it is clear that class limits in a table do not define all aspects of

FACILITY MONITORING control and risk assessment. Class limits are an important measure of environmental control, but if the only concern is passing the location then there could still be exposure to unseen risk. And, in this case, a risk that directly correlates to product quality and public safety.

Regardless of what changes may be made to ISO 14644-1, every indication is that it is unlikely EU GMP Annex 1 will follow suit. EU GMP Annex 1 was introduced to provide better guidelines for the life science industry and to address shortcomings of an ISO standard that focused on generic cleanroom requirements. ISO/DIS 14644-1.2, Annex C recognizes needs beyond what is included in the standard, as it specifically addresses those processes where particles greater than 5 μm (macroparticles) are important.

Certification and monitoring of the > 5 μm channel will continue to be an important element of control and risk assessment in the life science industry. This thesis is broadly supported among all international GMP standards that specifically relate to pharmaceutical and biotechnology sterile production. From a risk management perspective, is it prudent to give up a tool that focuses attention on changes in the environment that may serve to

July/August 2015 • www.cemag.us

alert personnel of a potential problem that could affect the quality or safety of the product? If using a conservative model when making a risk assessment, most will conclude, based on past experience and an understanding of microbiological organisms, that dispensing with 5 μm monitoring in the life science industry is simply imprudent and not worth the risk.

References • • • • •

ISO 14644-1: 1999 ISO 14644-2: 1999 ISO/DIS 14644-1.2:2014 ISO/DIS 14644-1.2:2014 EU GMP Annex 1, Nos. 4, 5 (page 3), No. 13 (page 4) • Farquharson, Gordon J., “Revision of ISO 14644-1:1999 — A progress report and explanation of some of the key issues and principles,” June 2012.

Jim Strachan is the Sales and Marketing Manager and Randy Grater is the Technical Services Manager for Climet Instruments. The company manufactures airborne particle counters and microbial samplers for the life science industry and other markets. www.climet.com

9

10 CLEAN ENVIRONMENTS

Modular Cleanroom Systems: A discussion of the four main styles of modular cleanrooms.

Wayne McGee PortaFab Corp.

Bulkheading capabilities for tools and equipment.

W

hether it’s because of advances in science and technology, growing regulation, or increased competition, companies and organizations throughout the world continue to face greater needs for controlled environments in their facilities. Oftentimes these needs arise very quickly and require solutions that can be implemented in a very timely manner. Such situations have spurred growth and innovation in the development of new modular cleanroom systems. Today’s facility operators can now choose from numerous modular systems to match their particular needs.

Regardless of which type of modular system one chooses, the benefits of these systems have remained relatively consistent over the years. They feature a quick and clean installation process, consistent product quality, reduced construction time, certain tax advantages, and “green” benefits resulting from a reduced material waste. As the market evolves, however, new systems are being designed for specific applications and industries.

The variety of panels and interchangeable components to choose from grows as well.

In today’s market, modular cleanroom systems can typically be categorized into four main styles: softwall cleanrooms, structural post and panel systems, specialty systems which include framing or partitioning, and aseptic systems. Each of these systems were designed by modular cleanroom manufacturers in order to satisfy the particular needs of an industry or application.

Softwall cleanroom systems Softwall cleanrooms provide an economical solution to applications requiring light environmental control.

These cleanrooms are typically comprised of a metal framing system, flexible vinyl curtain walls, and a number of fan filter modules at the top of the structure to control particulate and air flow. Due to their basic design, softwall cleanrooms can be erected very quickly with minimized labor requirements, offering an ease of mobility that other structures do not provide.

Advances in mounting methods, closure, and fastening systems have made it easier to incorporate softwall cleanrooms into a variety of applications as well as within other cleanroom systems. They can be utilized within larger cleanroom environments as partitions to separate areas or to create cleaner interior zones. As softwall systems continue to evolve, many manufacturers now offer transparent, tinted, opaque, and anti-static curtain options, furthering the list of applications for which these structures can be used.

Softwall cleanrooms offer a flexible and economical solution for lower level classifications and basic environmental control pertaining to GMP rooms, inspection rooms, manufacturing areas, and machinery enclosures.

Structural post and panel systems The core product for many modular manufacturers and suppliers consists of an “all-purpose” system that can be utilized for a variety of applications from GMP rooms to specific ISO classes. These systems offer a high level of versatility and can be used to outfit existing facilities or to create larger freestanding envelope structures to house separate compartmentalized processes.

These cleanroom systems can offer further flexibility by incorporating a panel-post design. This type of configuration offers the integration of a variety of different wall panels and cores including aluminum honeycomb, polystyrene, stainless steel, fiberglass reinforced plastic (FRP), and other selections based on the intended application and needs of the cleanroom.

All-purpose cleanroom systems are used in a variety of applications and ISO classifications including quality control enclosures or inspection rooms, medical device packaging areas, USP 797 compounding labs or equipment, and machinery enclosures.

July/August 2015 • www.cemag.us

11 xx

An Evolving Industry Framing/partitioning systems Due to the critical environmental conditions that are demanded in precision microelectronics manufacturing and nanotechnology applications, cleanrooms in these industries have typically required systems that integrated well with the equipment needed to run these operations.

Framing systems tended to be the ideal solution for these types of cleanrooms. These systems feature both vertical and horizontal members that easily connect to each other to simplify bulkheading and create air tight seals around equipment and tooling. Plus, the non-progressive design allows for easy removal of the walls without the need to remove adjacent panels, framing studs, or ceiling grids.

One challenge is that cleanrooms in the microelectronics industry typically require anti-static wall panels that are also non-outgassing and non-shedding in order to completely eliminate the potential for contamination when working with electronic devices. The proven solution is honeycomb aluminum panels — they perform well, but they are very expensive. A lot of innovation in the industry has been focused on developing more cost effective solutions. By analyzing the design of the cleanroom, one can often find opportunities to integrate thinner wall panels and lighter weight frames that can significantly reduce the cost of the cleanroom without sacrificing performance or functionality.

Aseptic systems Due to the unique needs and requirements found within the biomedical, life science, medical device, and pharmaceutical industries, modular cleanroom manufacturers have developed systems exclusively for these markets.

Aseptic systems are designed to eliminate the potential buildup of particles and other contaminants along cracks, seams, and crevices within the environment. To accomplish this, they utilize radius coving along all corners of the room while incorporating flush windows, walls, ceilings, and floor systems to provide a completely seamless interior. To further reduce contamination, these systems feature durable and non-shedding wall panels consisting of uPVC coating and aluminum honeycomb cores which are designed to withstand the repeated cleaning and sanitization processes required by the pharmaceutical and medical industries.

In order to further meet specific regulations or requirements, many modular manufacturers now offer a variety of interchangeable window, floor, and ceiling styles that can integrate seamlessly within the aseptic cleanroom design.

Further advantages for facility owners Most modular cleanroom manufacturers design their systems so that that they integrate well together, offering end clients further advantages by mixing and matching varying systems and components to create customized solutions. This type of integration between varying modular products allows facility managers to specify systems that are designed to meet the particular needs of their operation. For instance, a food manufacturer can be provided with a new laboratory, mixing operation, packaging line, and storage area, and still have these systems integrate together to form one cleanroom facility for increased throughput within the manufacturing plant.

Even within these systems, modular manufacturers are continuously identifying cost-savings opportunities for their end clients. Many can offer thinner cleanroom wall panels to be used as cladding to skin existing walls or create side wall returns and mechanical chases quickly and more economically. Interior walls that do not require bulkheading can be constructed from more economical cleanroom partition systems, as opposed a more expensive cleanroom panel specifically designed for bulkheading and tooling needs. Load-bearing structures can also offer financial benefits by allowing the placement of air filtration equipment on top of the cleanroom. This arrangement eliminates the need to create bay and chase areas to surround the environment, significantly reducing costs.

A continued evolution For those that have not considered utilizing modular cleanrooms in a while, it may be time to revisit them as an option. Newly designed modular systems and components are increasing in functionality and reducing overall costs as systems are becoming more applicationspecific and less “one-size-fits-all.” As a result, today’s facility managers have more and better options to choose from when comparing modular systems as the industry continues to evolve.

Wayne McGee is President and CEO of PortaFab Corp., a manufacturer of modular cleanrooms and environments, with over 25 years of modular design and construction expertise. PortaFab is headquartered in St Louis, Mo. www.portafab.com

Cleanroom showing partition walls and custom options including pass through cut outs and window glazing styles.

12 CLEAN OPERATIONS

The Cleanroom’s Dirty Little Secret Protection is a two-way street.

Don Cronk Ansell

Hazards in cleanroom environments require special types of PPE, such as the TouchNTuff 83-500 for chemical protection.

ost of the time, the “protection” part of hand protection is straightforward.

Gloves are designed specifically to protect the wearer’s hands from some type of injury — cuts, spills, burns, or even repetitive use injuries that only manifest over time. The challenge is as straightforward as finding the right glove for the job — balancing comfort, performance, and protection.

In cleanroom environments, however, it isn’t so simple. These are delicate ecosystems dedicated to research and manufacturing that are sensitive to

M

even minute impurities, and 80 percent of those impurities originate from people. 1 Gloves and other personal protective equipment must limit the introduction of any particulates into the cleanroom, which means these special-use gloves are designed to protect the products as much as the wearer. Consider the potential cost of a contaminated pharmaceutical product; millions of dollars could be conservative.

With that in mind, let’s take a closer look at hand protection for cleanrooms from both perspectives — providing protection for the wearer and for the product — and how glove technologies and design practices are addressing both needs.

Protecting the product Of course, there are several types of cleanrooms. A cleanroom designed for assembly of microchips for electronics is different than one designed for medical research, and the level of cleanliness required in the rooms is dependent on the activities taking place inside. In the U.S., cleanrooms are designated Class 1; Class 10; Class 100; Class 1,000; Class 10,000; or Class 100,000, corresponding to a certain acceptable number of particulates per cubic foot. The lower the number, the cleaner the room. In Europe, this designation follows ISO numbering guidelines (ISO 1 to ISO 9), again with the lower number representing the cleaner room. As you might expect, gloves and other PPE designed for Class 1, Class 10, or Class 100 rooms — sometimes referred to as ultra-cleanrooms — are more carefully manufactured, packed, and shipped than those carrying less sensitive classifications.

It’s interesting to note that while there are industry standards that establish the maximum number of particulates allowed per cubic foot in cleanrooms with different designations, there are no standards or regulations around cleanroom PPE or glove performance. When choosing gloves for use in a cleanroom, buyers should therefore carefully check that the particle count of the gloves does not exceed the standards of the cleanroom where they will be used. For example, gloves for use in a Class 10 cleanroom should carry particle counts no higher than 850 — that’s the number of particles 0.5 microns or smaller. An acceptable

July/August 2015 • www.cemag.us

number for Class 100 is 3,000. Again, those numbers are recommended, not regulated.

Another concern is ionic content — the measure of the amount of residual ions, either positive or negative — on the gloves. Non-volatile residue, or NVR, is a potential contaminant with various implications to products or activities. Silicone, for example, can’t be present in aerospace manufacturing in a cleanroom environment because it can impact the effectiveness of some adhesives. Sodium ions can cause conduction and low field breakdown in semiconductor manufacturing, while chlorides can trigger corrosion in disk drive manufacturing.

Ionic residuals and the insulative properties of the base glove material also dictate how well a material behaves in terms of electrostatic discharge (ESD) — another important consideration in the cleanroom, especially in the electronics sector.

Since natural rubber latex is an excellent insulator, it isn’t viable for ESD-sensitive applications.

Remember what happened when you rubbed a balloon over your hair when you were a kid? Not what you want in a cleanroom dedicated to the assembly of sensitive electronics. A nitrile glove is by far the better choice.

Protecting the person While preserving the sanctity of the cleanroom is an important component of glove selection, it can’t take precedence over the safety and protection of the worker. Cleanroom hazards fall into three categories: physical, biological, and chemical, each of which requires unique characteristics from a glove.

Most physical hazards are what you might expect — sharp or abrasive objects and surfaces that can cut, scratch, or penetrate the skin. These types of hazards can present a challenge in terms of glove design. Innovations in materials are improving durability in cleanroom gloves, but today true cut protection still requires wearing a cut-resistant glove under the cleanroom glove.

Biological hazards are common in aseptic manufacturing and research and include risks associated with handling potentially pathogenic materials.

Gloves for these tasks typically are thin, singleuse, disposable gloves designed to provide a reliable barrier between the biological agent and the skin. They are similar to surgical gloves, although cleanroom gloves — for any type of cleanroom environment — are always powder-free, for obvious reasons. Barrier efficacy or integrity for this type of product is evaluated by testing the gloves for pinholes. As with any mass-produced product, these gloves typically are held to a manufacturerdetermined acceptable quality level (AQL). This is

another metric informed decision-makers need to know before choosing a glove, understanding that the lower the AQL, the better quality the barrier.

Chemical hazards are different, because various chemicals and chemical compounds can react in different ways to materials used in gloves — and to the skin beneath those gloves. Workers in cleanrooms typically handle small quantities of hazardous chemicals, and most cleanroom gloves are designed appropriately, as single-use gloves focusing primarily on splash-resistance. This means the gloves are designed to provide initial protection when a chemical splashes onto the hands, giving the worker adequate time to remove and dispose of the glove immediately and don a replacement.

Ensuring protection without compromise There was a time when serving these two distinct needs — protecting the product and the person — wasn’t possible to the standards we find acceptable today. Fortunately, that no longer is the case.

Advanced materials and new design and cleaning processes ensure the availability of a glove that can provide adequate protection for the job without compromising the purity of the cleanroom.

While cleanroom gloves start out as any other typical single use glove they go through additional manufacturing steps to ensure they meet the rigorous requirements of cleanroom personal protective equipment. Those steps include multiple washing and leaching, or rinsing, cycles to remove production chemicals and thoroughly clean the finished gloves. The final laundering happens in a cleanroom itself, and those gloves then are bagged (or doublebagged) in vacuum-sealed plastic bags in yet another cleanroom. Truly sterile gloves go through a sterilization process involving irradiation after cleaning and packaging. It’s an expensive, time-consuming process and some manufacturers may cut corners.

Responsible decision-makers should ask questions about the cleaning and packaging processes used by their cleanroom glove manufacturer.

Cleanroom gloves must protect not just the person wearing the gloves, but the cleanroom environment itself and the products within that environment. Today’s technologies make it possible to mitigate all of these risks.

References 1. http://www.slideshare.net/HeidiTuomi/r3-naantali Don Cronk is the Regulatory Affairs & Technical Services Manager for Ansell’s Single Use Global Business Unit. www.ansell.com

13

14 CLEAN APPLICATIONS

Cleanroom Design and Environmental The RFAB semiconductor facility of Texas Instruments.

Ben Winsett Texas Instruments

ne of the most recent semiconductor fabrication facilities added to Texas Instruments’ lineup of 12 worldwide wafer fabs is located in Richardson, Texas. Aptly named RFAB for short, the fab’s list of industry firsts and achievements in next-generation cleanroom design are much longer.

RFAB is the world’s first LEED-Certified semiconductor manufacturing facility, featuring several designed-in technologies that allow for more sustainable cleanroom operation and low cost environmental control.

O

paramount, the design team was tasked with building a factory at 30 percent lower cost than a similar 300mm wafer fab located just six miles away. Though construction was completed in 2006, the first wafer was produced from the site in 2010.

At a high-level, the fab consists of two-level fab construction; an open-floor, flow-through ballroom design (minimal columns, waffle slab, common plenums) spanning 284,000 sq. ft.; and cleanroom environmental control equipment including fan filter HEPA units at 25% coverage, mini-environment for all tools and sealed wafer carriers (FOUPs), makeup air systems to control dewpoint and pressure, cleanroom sensible cooling coils to control temperature, ionizers to mitigate static electricity in stockers, incoming, and wet chemical areas, UV sleeves for cleanroom lights in photolithography to filter wavelengths below 520nm, real-time airborne molecular contamination systems

Environmental control technologies and techniques

RFAB includes a minienvironment for all tools and sealed wafer carriers (FOUPs).

The fab’s features include: • Well-insulated and airtight construction to maximize energy efficiency at the building envelope; • High-efficiency fan filter units (FFUs) to recirculate and remove particles from the cleanroom air stream; • Run-around coils on the make-up air systems, which allow more efficient use of heat exchange systems to minimize the reheating requirement when dehumidifying outdoor air; • Extensive use of larger and straighter pipe and ductwork to reduce inherent pressure loss/restriction, thereby enabling installation of smaller, lower cost, more efficient pumps and fans; and • Gravity-driven waste streams achieved through proper layout and upfront planning. Theseeliminate the need for lift stations and reduce potential impact from airborne molecular contamination (AMC).

The inception of RFAB and construction of the LEED-Certified semiconductor manufacturing facility began in 2004. Not only was focus on sustainability

It is easier to list the parameters and conditions that have no impact on the semiconductor manufacturing process than it is to detail those that do. However, all of these parameters fall into two general categories for cleanroom environmental control. The first are parameters with absolute control requirements such as cleanroom differential pressure, particle counts, static electricity, and exposure to UV light. The second are parameters with both absolute and rate-of-change/ stability control requirements such as cleanroom temperature, dewpoint, and AMC. Sustainability and cost efficiency were the fundamental design criteria for RFAB; therefore, the basic configuration chosen was a ballroom concept to maximize space utilization. When it came to choosing the required cleanroom classification, the predominant trend at the time had paced toward cleaner and cleaner classifications for the main cleanroom area.

RFAB cleanroom design departed from that scheme, opting for a fully automated factory, sealed wafer carriers, and tool mini-environments. If the wafers are only exposed to an air stream inside the manufacturing tools, there is no need to operate a cleanroom at Class 1 levels. Instead, each tool has a HEPA filtration system allowing it to achieve Class 1 capability while the ballroom can operate at Class 100 or higher. This change

July/August 2015 • www.cemag.us

15

Control Technologies significantly reduced the recirculation air flow rate and number of FFU’s required to maintain cleanroom particle spec. The benefits do not stop there; reducing recirculation air flow rate reduces motor power, which in turn reduces sensible heat load, which significantly reduces the requirement for heat rejection equipment such as cooling towers and chillers. Furthermore, the ballroom design concept, coupled with FFUs, generates a negative plenum that further minimizes risk of particle contamination caused by ceiling penetrations and leaks in exterior seals. Particle contamination is arguably the largest concern in maintaining a controlled cleanroom environment; however, the choice does not have to be between improved control and reduced operating cost or equipment.

In addition to these technologies and techniques, several unique solutions were employed at RFAB to achieve improved environmental control and low-cost sustainable operation: • Split chiller plant concept where a smaller portion of the chillers are designed for the cleanroom dehumidification load, operating at a nominal 42 degrees F. The remaining chillers operate at higher discharge temperature better suited for sensible cooling and in a heat recovery configuration, significantly reducing the requirement for natural gas fired boilers and water consumption at cooling towers.

• Adiabatic humidification systems eliminate the need for steam boilers or electric humidifiers, resulting in a simple, well controlled cleanroom humidification system that reduces water consumption and sensible cooling demand year-round.

• Full utilization of variable speed drives (VFDs) on all cleanroom control systems provides the ability to match demand as efficiently as possible while maintaining installed system capacity. VFDs are the primary means of controls for cleanroom pressure and air recirculation flow rate.

• Real-time AMC detection equipment allows fab personnel to pinpoint components, systems, or outdoor conditions generating chemical vapors that can cause significant impact and corrosion to wafers being processed. Though it was not by design, allowing RFAB to remain empty for several years after construction permitted all the materials within the factory to offgas completely and achieve the fastest initial product qualification period of any factory at TI. It is similar to a “new car smell” that is given the time to fade away.

• An extensive network of sensors integrated into a real-time data acquisition system with historical trending allows both the Facilities and Fab personnel to receive alerts on any adverse conditions so they can be corrected immediately. In addition, this system provides immediate feedback for setpoint changes and optimization opportunities, enabling validation of expected results and data driven decisions for sustaining operations and environmental control.

Outlook for future cleanroom design Based on the advances at RFAB and progression in cleanroom design, concepts that will likely be pursued in future cleanroom designs include: • Further reduction in smocking requirements, which would allow for more relaxed temperature, humidity, and particle specifications, thereby generating opportunities for further utility reduction via recirculated air reduction and seasonal cleanroom temperature and dewpoint adjustments.

• Large-scale general exhaust or heat exhaust recovery either directly for fresh air makeup, or through technologies such as desiccant systems or enthalpy wheels.

• Full scale implementation of adiabatic humidification system offsetting sensible cooling load and providing improved humidification control.

• Lighting upgrades to longer life, reliable LED products, and responsive lighting systems. More automation results in fewer personnel required to perform manual tasks on the cleanroom floor, which reduces the need for active lighting in many areas.

• Continued use of ballroom cleanrooms for long term operational flexibility and better space utilization.

• Adoption of inexpensive wireless sensors that could allow for better monitoring, control, and system optimization.

• Continued improvement in AMC control through continuously purged FOUPs (inert gas), further automation, and overall focus on wafer environment instead of cleanroom environment. continued on pg. 23

Completed cleanroom (ballroom design) prior to installation of production equipment.

16

STANDARDS AND PROCEDURES

Personalized Medicine, Companion Diagnostics, and NGS Diagnostic Tests T Bikash Chatterjee Pharmatech Associates

he field of personalized medicine has been evolving ever since the Human Genome Project1 was completed in 2003. During that program researchers identified specific genes linked to particular disease states such as the MSH2 gene with colon cancer, and variations in the FAD gene linked to Alzheimer’s disease. Personalized medicine looks to exploit this information by tailoring drug therapies to a patient’s gene mutation. To do this requires a diagnostic test for use by physicians to identify candidates for therapy and, specifically, what the proposed customized therapy should be. Termed Companion Diagnostics

by FDA, the agency issued its first guidance2 in August 2014 to begin to define what constitutes a companion diagnostic and its regulatory path for filing.

FDA Companion Diagnostics Guidance The FDA guidance is intended to help companies identify the need for these tests during the earliest stages of drug development and to plan for the development of a drug and a companion test at the same time. The guidance finalizes and takes into consideration public comments on the draft guidance that FDA issued in 2011.

The guidance makes several important clarifications for in-vitro diagnostic (IVD) developers and drug developers. One point states that an IVD is considered a Companion Diagnostic when the IVD is essential to the safe and effective use of the therapeutic product. The key term in this definition is “Essential.” The notion of essential is defined in footnote 6 (emphasis is mine): “When use of a diagnostic device is required in the labeling of a therapeutic product (e.g., for selection of appropriate patients for therapy, or to select patients who should not use the product, or for monitoring patients to achieve safety or effectiveness), use of the diagnostic device is considered ’essential’ for the purposes of this guidance. Uses of diagnostic devices that are suggested but not required in therapeutic product labeling are not considered ‘essential.’”

This definition answered some questions but raised others. Specifically, are personalized drug therapies that require a companion diagnostic considered a combination product in the eyes of the FDA? The guidance further addresses this question in footnote 5: FDA expects that most therapeutic product and IVD companion diagnostic device pairs will not meet the definition of “combination product” under 21 CFR 3.2(e). It is not necessary to contact the Office of Combination Products about whether a therapeutic product and IVD companion diagnostic device pair is a combination product unless recommended by CDER, CBER, or CDRH. FDA intends to require separate marketing applications for a therapeutic product and an IVD companion diagnostic device intended for use with that therapeutic product regardless of whether the products could constitute a combination product.

So basically the agency is stating that if the drug and diagnostic requirement meet the definition of a combination product, they will require separate regulatory submissions. However, the FDA is willing to consider a single submission combination drug on a case by case basis.

The need for a companion diagnostic clouds the regulatory pathway for personal medicine innovators because the development timelines and skill sets are quite different for drug development and IVD development. It is quite possible that a novel drug therapy could be hung up waiting for the development of its companion diagnostic. Further confusing the issue is the FDA’s desire in most cases to have the diagnostic complete before the drug therapy, although they have indicated they are willing to discuss this expectation on a case by case basis.

Next generation sequencing diagnostics (NGS) Almost all current FDA-approved in-vitro diagnostic tests (IVD) measure only a single or a limit-

July/August 2015 • www.cemag.us

ed number of substances, such as DNA or proteins.

Thus, it may require several patient samples and several tests to evaluate a patient’s clinical status or to determine the best therapy for the patient.

In contrast to current approved IVDs, NGS diagnostics can detect over three billion bases in the human genome and may identify almost three million genetic variants in a single test. It is possible that a single NGS test could identify multiple disease states, making it difficult for the FDA to evaluate the suitability of the test. Because an NGS can analyze the whole genome, it is not necessary to know what variant you are looking for. The FDA has issued a white paper regarding NGS diagnostics and held a public workshop in February 2015 to discuss the regulatory paths forward. The FDA has approved one NGS system based upon demonstrating analytical capability and reliability in detecting a subset of variants in the genome. This approach is discussed in the white paper and is a possible way to prove reliability and capability. In the white paper the FDA asked 10 basic questions to help frame the discussion at the workshop to obtain a clearer picture of what is a fair and reasonable regulatory requirement.

17

DeviceRegulationandGuidance/ GuidanceDocuments/UCM262327.pdf Bikash Chatterjee, President and Chief Science Officer of Pharmatech Associates, has been involved in the biopharmaceutical, pharmaceutical, medical device, and diagnostics industry for over 30 years. His expertise includes site selection, project management, design, and validation of facilities for U.S. and European regulatory requirements.

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Personalized medicine has the potential to be the biggest advance in health in many decades.

To fully realize its promise will require shifting the paradigm as to how we define quality, efficacy, and safety, for both personalized drug therapies and their companion diagnostics.

The FDA is continuing to refine its position on Companion Diagnostics and is working on more detailed guidance. But the agency must consider the broader implications to Laboratory Derived Tests (LDTs) within the guidance. Wall Street has bet heavily on this particular sector of biotech, creating some of the largest IPOs of 2014 and 2015. Whether the FDA and industry can navigate this complex relationship between performance, measurement, and safety will determine the likelihood of its realization.

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References 1. Human Genome Project: http://web.ornl. gov/sci/techresources/Human_Genome/ index.shtml 2. http://www.fda.gov/downloads/MedicalDevices/

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18 CONTAMINATION CONTROL IN AND OUT OF THE CLEANROOM

Particles Cling to der Waals G

Barbara Kanegsberg and Ed Kanegsberg BFK Solutions LLC

eckos appear to defy gravity as they run up a wall or across a ceiling. How can they do that? It is not by exuding some sort of sticky goo. It is due to force, the same kind of force that causes a particle or soil to adhere to the surface of a component being manufactured or used, or to tooling, or to cleanroom surfaces.

Three molecular forces — polar, hydrogen bonding, and dispersion — are associated with adherence as well as with solvency and cleaning.1 Geckos stick to walls by exploiting dispersion force.2 Dispersion force — sometimes referred to as a non-polar, Van der Waals, or London force — is the weakest of the three, but it may be the most fascinating as well as the most significant for particle adhesion and critical cleaning. Dispersion force is the mechanism by which nonpolar compounds liquefy or solidify.

Subtle power Polar and hydrogen bonding forces are associated with molecules that have dipoles, permanent positively and negatively charged sides. Dispersion forces, however, are a property of all molecules whether or not they have an inherent dipole. Because the electrons are always in motion, there can be a momentary fluctuation during which more of the electrons are on one side of the molecule than on the other.

When this happens, the side with more electrons becomes

momentarily negatively charged and the other side becomes positively charged, creating a momentary dipole.

If another molecule comes very close to the molecule with the momentary dipole, the electrons on the approaching molecule will be induced to move. For example, if the momentary dipole has its positive side nearest the approaching molecule, electrons will be drawn towards that side creating a dipole in the second molecule. This sets up an attractive force between these two molecules.

Sometimes, the two colliding molecules do not have enough energy to overcome this force and bounce back away; the molecules “stick” together.

From this point, the dipoles are no longer momentary; they will last as long as the molecules are bound together.

Moreover, this molecular duo is itself a dipole that can attract additional molecules, in somewhat of a chain reaction or domino effect.

Gecko feet The feet of geckos have millions of extremely tiny hairs.

The ends of each hair subdivide into many tiny pads or spatulae (about 0.2 µm diameter), each of which induces dipoles and associated attractive dispersion forces on molecules of the wall surface.

Although dispersion forces are exceedingly small, the collective sum from all the spatulae, or even those on a single toe, is sufficient to support the

gecko’s weight, even on a very smooth surface.

Particles and dried soils

Dispersion force is also a primary mechanism that causes contamination to stick. For dispersion forces to be attractive or adhering, the molecules have to be very close, essentially within one atomic diameter of each other — just a few nanometers. Small particles fit more easily into the pits and crevices of a surface (most surfaces are rather rough at a microscopic level even if they look smooth), just as gecko feet hairs do, so that more of the molecules of the particle are within the distance for attraction to the surface molecules. This is why small particles that stick to a surface are more difficult to remove than large ones.

A similar explanation elucidates why soil that is allowed to dry onto a surface is more difficult to remove. When a liquid that has soil molecules in suspension evaporates, the soil molecules become close enough to the surface for attractive dispersion forces to hold them there. Once the attractive bond between molecules is made, it takes additional force to overcome and break these bonds to allow the soil to be removed.

This is why we keep reminding you that deferring cleaning until the product wends its way through the supply chain over to your cleanroom is a terrible idea. Critical cleaning may need to happen early on in the build process.

July/August 2015 • www.cemag.us

Contamination control

References

When it comes to achieving, monitoring, and maintaining a clean surface, it is important to consider both the number and the size of particles.

The presence of many large particles might pose less of a problem than a few very small ones.

Large particles are easier to filter out of air or liquids. Also, because they will not adhere as strongly to a surface, they are also easier to remove during a cleaning process.

Small particles can be a bigger challenge, both in terms of filtration and cleaning.

Because a molecule can be thought of as the ultimate small particle, airborne molecular contamination (AMC) deserves additional attention, both in cleanroom monitoring as well as control.3

1. J. Burke, “Solvents and Solubility,” Handbook for Critical Cleaning: Cleaning Agents and Systems; B. Kanegsberg and E. Kanegsberg, editors; CRC Press, 2011.

2. K. Autumn et. al. “Evidence for van der Waals adhesion in gecko setae.” Proceedings of the National Academy of Sciences of the USA, 2002, 99, 12252-12256. http:// www.pnas.org/cgi/content/ full/99/19/12252 3. B. Kanegsberg and E. Kanegsberg, “Airborne Molecular Contamination, Part 1: Silent Poison,” Controlled Environments Magazine, June 2009. http://www.cemag.us/ articles/2009/06/airbornemolecular-contaminationpart-1-silent-poison

Barbara Kanegsberg and Ed Kanegsberg (the Cleaning Lady and the Rocket Scientist) are experienced consultants and educators in critical and precision cleaning, surface preparation, and contamination control. Their diverse projects include medical device manufacturing, microelectronics, optics, and aerospace. info@bfksolutions.com

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20 BENCHES AND ENCLOSURES

Laminar Airow Isolator

Enclosures for Robotics and Laboratory Automation HEMCO Enclosures are designed to enclose robots and other lab automated processes by providing exhaust air systems or HEPA filtered clean workstations.

Enclosures are built to protect robotic processes from contamination and personnel from hazardous fumes. A selection of standard sizes in vented or HEPA filtered models is available. www.hemcocorp.com

Swing-Over Bench RPA Cleanroom Products offers Palbam Class Cleanroom Gowning Systems and Swing-Over Bench. The system provides a seating surface and a raised platform to assist with putting on booties or shoe covers. A protective barrier exists between the controlled and uncontrolled sides of the gowning area. Modular components that can be arranged in linear or angular configurations.

The unit features electropolished stainless steel construction. www.rpaproducts.com

Clean Benches and Workstations The clean bench and workstation models available through Clean Rooms International incorporate either HEPA or ULPA air filtration systems. Table top, stand-up, and sit-down versions are offered, in a variety of vertical and horizontal flow combinations. Products are designed to accommodate the most stringent cleanroom conditions as well as systems engineered for applications requiring a lower level of cleanliness. www.cleanroomsint.com

The Esco General Processing Platform Isolator is suitable for aseptic handling processes, including compounding and filtration, filling/stoppering/ crimping, sterility testing, weighing and dispensing, and other processes that require an ISO Class 5 (Grade A) aseptic environment. The control system allows the operator to select positive or negative chamber pressure as well as single pass or recirculating airflow. It also features supply and return ULPA filter safe change capabilities. www.escopharma.com

July/August 2015 • www.cemag.us

21

Wet Bench

Liquid Workstation LEWA Process Technologies Inc. offers its Bulk Liquid Bottling Station, a single pass laminar flow cleanroom work station. The unit minimizes operator involvement, and provides an isolated filling environment that smoothly fills containers from the bottom up. The filling operation is controlled using an automated arm and scale system. A freestanding vertical laminar air flow hood isolates the filling environment from the cleanroom and the operator. www.lewapt.com

Aseptic Containment Isolator Comecer’s aseptic containment isolator is suitable for antiblastic and chemotherapic compounding. It is comprised of a compact air lock chamber and a 4-glove process chamber (2 or 3 gloves also available).

The system is equipped with a unidirectional airflow with positive/ negative pressure with respect to the lab environment. The airlock is equipped with turbulent airflow for flash bio-decontamination. www.comecer.com

Ductless Fume Hood Air Science offers the Purair ECO line of Energy-Saving Ductless Fume Hoods designed for both chemical and particulate protection. The units are available with a choice of controllers including touchpad control with color display interface. An optional BACnet network interface connects all cabinet control, monitoring, and alarm functions to an open-source facility monitoring system. www.airscience.com

The Two Process Wet Bench from Leatherwood Plastics features a sloped sump area with drain, hinged clear PVC eye shield, and rear side exhaust connection with adjustable slot openings to maintain a fume controlled work area. Other features include a purged control enclosure, removable work deck sections, adjustable levelling legs for a balanced and stable set up, and low profile casters. www.leatherwood.com

Vertical Flow Bench

Hutchins & Hutchins Inc. distributes Cleanroom International’s E Series Vertical Flow Clean Benches. The self-contained SAM Fan Filter Unit provides Class 100 HEPA filtered air, flowing in a vertical laminar pattern. The work surfaces are solid core with a white, high pressure laminate finish. The HEPA filters are 99.99% efficient at 0.3 micron or larger with anodized aluminum frame. www.yourcleanroomsupplier.com

22

ASK JAN

Cleanroom Training e built an ISO Class 7 cleanroom to serve our customers in the aerospace industry. We’ve hired engineers and operators to work in the cleanroom.

Where can we resource training for our cleanroom personnel?

There are several independent cleanroom and contamination control consultants and trade industry conferences that you may contact to provide the required training. However, the cleanroom and controlled environment industries rely on two main sources for standards and best practices in cleanroom and contamination control management: the Institute of Environmental Sciences and Technology (IEST) for training best practices, and the International Organization for Standardization (ISO) for global standards.

The ISO 14644 global cleanroom standards established airborne particulate cleanliness classes for particle sizes ranging from 0.1 µm to 5 µm as well as design, construction, and operation of cleanrooms, minienvironments, and separative devices. Eight of these international standards are currently designated by the American National Standards Institute (ANSI) as American national standards. IEST is Secretariat of ISO/TC 209 and Administrator of the ANSI-accredited U.S. Technical Advisory Group (TAG) to ISO/TC 209. IEST is a not-forprofit organization that provides cleanroom and contamination control training to promote education and best practices. For more than 15 years, IEST has provided one-day courses on the ISO 14644 series of cleanroom standards during the annual technical meeting (ESTECH) in the spring; the Fall Conference; at IEST headquarters in the northwest suburbs of Chicago; and custom training at locations in the U.S. and other countries.

IEST also develops Recommended Practices (RPs) for the nanotechnology; contamination control; design, test, and evaluation; and product reliability industries. IEST is an ANSIaccredited standards developer and all the educational programs are peer-reviewed. The senior faculty members of the Education Advisory Council are industry subject matter experts who

W Jan Eudy Cleanroom/Contamination Control Consultant

have contributed information to the current IEST recommended practices and ISO 14644 series of standards. IEST also offers educational training on recently published recommended practices in the disciplines listed previously.

The ISO standards provide the information as to “what to do” and the IEST recommended practices provide the information as to “how to do it.” Together, these non-profit organizations contribute a vast amount of knowledge and resources to the cleanroom and controlled environments industries.

Internationally, IEST (www.iest.org) is also a founding member of the International Confederation of Contamination Control Societies (ICCCS) (www.icccs.net). The ICCCS was formed in 1974 and consists of 20 countries as part of 17 member societies. The objectives of the ICCCS are to promote best practices through the international exchange of knowledge and the coordination and promotion of standards.

At the core of ICCCS is education, and the ICCCS encourages the promotion of education and training through coordination with member societies such as IEST. The International Cleanroom Education Board (ICEB) is the education arm of the ICCCS and prepares guidelines for contamination control courses for international harmonization through accreditation. IEST is considering providing hosting within the U.S. of ICCCS accreditation courses to expand global harmonization of contamination control education.

The ICEB program operates under a number of guiding fundamental principles. One is the principle of “personal certification through examination,” meaning the emphasis is on the student and not the company. Another principle is the 75/25 rule, stating that a minimum of 75 percent must be based on an ISO cleanroom standard (which is the same across the world) and 25 percent can be localized to suit different industries to allow flexibility. Since the ISO standard is the same everywhere in the world, the goal is to train people applying the standard to have the same competency skills and expectations.

July/August 2015 • www.cemag.us

Yet, there are specific needs — such as within the aerospace community — that require flexibility in providing application-specific training. The longer term objective of IEST and the ICEB is to create common training programs to improve professional skills with globally accepted accreditation based on recognized standards.

The author acknowledges and thanks IEST staff and Conor Murray for their contribution to this article. Conor Murray is a principal in his own company, 3dimension Cleanrooms, and is a subject matter expert on cleanrooms and contamination control. He is Chairman of the Irish Cleanroom Society and Head of Delegation for Ireland at TC 209. He is a past Chairman of the ICCCS and the inaugural chair of the ICEB. Jan Eudy is a Cleanroom/Contamination Control Consultant as well as a Fellow and Past President, Institute of Environmental Sciences and Technology.

She is located in Carolina Beach, N.C. and can be reached at janeeudy@gmail.com.

23 17

Cleanroom Design and Environmental Control Technologies continued from pg. 15

Summary Semiconductor manufacturing requires significant energy, resources, and monitoring to ensure product quality and personnel safety. Turning a normal environment, where everything is a risk to the wafer, into a highly controlled, stable, continuously operating environment is a unique challenge. However, that challenge can be met without sacrificing cost or environmentally sustainable operation. RFAB is a testament to bringing the best of both worlds together to achieve the world’s first LEED-Certified semiconductor manufacturing facility.

Ben Winsett is the Facilities Engineering Manager of Texas Instruments, headquartered in Dallas. www.ti.com

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24 HOW IT WORKS

July/August 2015 • www.cemag.us

Cleanroom Wipe Dispenser Improves Process in Controlled Environments next wipe in the stack untouched and exposed enough to easily pull from the maceutical, biomedical, microelecdispenser. tronics, and similar industries, it is The Grab-EEZ is an ESD-safe, wallimperative that exposure to micromountable or table top cleanroom bial contaminants and electrostatic wipe dispenser. Its rectangular shape discharge (ESD) are minimized at features a compartment for storing every turn of the manufacturing wipes protected from chemicals and process. To maintain an exceptionalother outside contaminants found in ly “clean” environment, tabletops and cleanroom settings. A viewing slot other hard surfaces must be regularly along a substantial portion of the wiped down with cleanroom wipes. dispenser is present so that a user Normally, cleanroom wipes are supmay visually determine when the plied in flat sheets and placed on wipes within the compartment a table or in trays within a cleanbecome depleted. room. Because the facility personThe outer housing of the wipe nel is required to wear gloves, it is dispenser is comprised of an ESDvery difficult to select one wipe at resistant material. One particular a time. Consequently, sometimes issue with ESD-safe cleanroom three or more wipes are selected wipes when they are pulled — resulting in wasteful usage and from the bag, although the the possibility of cross-contaminawipe itself may be ESD-safe, the tion. bag can contain static electricity which is harmful to a cleanroom Modifying the that produces microelectronics. process of selecting a cleanroom This method of distribution wipe is often not the top priority of Each cleanroom wipe is stacked with prevents cross contamination cleanroom personnel. Yet, as waste the v-fold seam exposed in the opening by removing the option to continues and valuable counter of the unit, leaving the next wipe in the select more than one wipe at a space is taken up by a messy stack stack untouched and exposed enough to time. In addition, the efficient easily pull from the dispenser. of wipes, that modification might delivery eliminates the need be worth a second look. to “fan” through a stack of wipes and saves time Similar to the benefits a napkin dispenser offers a — resulting in reduced cost of consumables and busy fast food restaurant, the Grab-EEZ from Highoperating cost.

Tech Conversions provides these same benefits to Each dispenser is prepared and cleaned in a cleana cleanroom. Unlike a napkin dispenser used in a room and double bagged before it is first introfast food restaurant, a well-designed cleanroom duced into the controlled environment where it will wipe dispenser has to be carefully engineered usbe used. The Grab-EEZ is made from the highest ing advanced nonwoven folding technology and grade ESD-safe plastics and is suitable for use in ISO cleanroom compatible materials.

Class 5 (Class 100) cleanrooms and higher.

At the heart of the Grab-EEZ design are its uniquely Cleanroom facilities that incorporate the Grab-EEZ folded wipes. Each wipe is uniquely folded in a Wipe Dispenser will notice improved organization double “C” shape. The wipe contains an upper and and reduced cross contamination, as well as cost savlower leg, wherein the lower leg of each cleanroom ings as a result of less waste. wipe abuts the upper leg of an adjacent wipe. Each More information is available at www.highcleanroom wipe is stacked with the v-fold seam techconversions.com. exposed in the opening of the unit, leaving the

Problem: Within the phar-

Solution:

25

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@CEMagazineUS

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Online Exclusive: Modular Cleanroom Design: The Worth is in the Details When cleanrooms are required, various design solutions are available. If modular cleanroom is chosen as the solution, numerous options must be taken into account. http://www.cemag.us/articles/2015/07/modular-cleanroomdesign-worth-details Courtesy of CRB

The Use of Modern Technology and the Internet for Hospital Monitoring

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Maximizing patient safety is at the top of every hospital administrator’s priorities list. http://www.cemag.us/articles/2015/07/use-modern-technology-and-internet-hospitalmonitoring

Check out the Most Popular News Stories on cemag.us • Comet Lander Finally Awakens The European Space Agency’s lander Philae has woken up after seven months in Courtesy of ESA hibernation on the surface of a comet. http://www.cemag.us/news/2015/06/comet-lander-awakens-potentially-advancing-science-20-years • NIH Shutters Drug Unit Due to Fungal Contamination The NIH Clinical Center suspended operations of its Pharmaceutical Development Section due to the discovery of serious manufacturing problems and lack of compliance with standard operating procedures. http://www.cemag.us/news/2015/06/nih-shutters-drugunit-due-fungal-contamination • Nearly Frictionless Motion Developed In tuning friction to the point where it disappears, the technique could boost development of nanomachines. http://www.cemag.us/news/2015/06/nearly-frictionlessmotion-developed

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26 CLEANROOM TIP & INDEX

OM

O CLEANR

July/August 2015 • www.cemag.us

Managing Energy Consumption

he cleanroom industry has embraced the tactic of including controls to allow the end user to manage the facility’s energy consumptions. This includes set back hours for non-critical hours of operation to save energy, as well as adjusting the facility’s air changes per hour (ACH) for the times that they might go out of specifications.

Some of the most common adjustments are made by tying in the facility’s fan filter units to be monitored and controlled by stand-alone control systems and, more commonly, the building management system (BMS). This is dependent upon the facility’s GMP and the critical environmental issues in the process.

T

USP 797, 798, and 800 call for these controls: • interlocking doors • lighting systems • particle counters • temperature sensors • pressure sensors • humidity sensors • closed loop operation of the listed equipment

This cleanroom tip is courtesy of Les Goldsmith of Envirco Corp. in Sanford, N.C. www.envirco-hvac.com

ADVERTISERS INDEX Arizona Polymer Flooring ...................... 25........................................ www.apfepoxy.com Berkshire Corporation ........................... 27........................................www.berkshire.com Clean Air Products ................................. 19............ www.cleanairproducts.com/resources Contec, Inc............................................. 28........................................www.contecinc.com Geerpres................................................. 9..........................................www.geerpres.com Mar Cor Purification .............................. 23.............................................www.mcpur.com Masy BioServices.................................... 2............................................... www.masy.com Monroe Electronics................................ 25........................www.monroe-electronics.com S-Curve Technologies ............................ 25...........................................www.s-curve.com

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Simplex Strip Doors, Inc. ....................... 19.............. www.simplexisolationsyystems.com TSI, Inc. ................................................. 17................................. www.tsi.com/lifescience Veltek Associates, Inc. ............................ 3..............................................www.sterile.com Controlled Environments Magazine® (ISSN #1556-9268, USPS #021-493), is a registered trademark of and published seven times a year by Advantage Business Media, 100 Enterprise Drive, Suite 600, Box 912, Rockaway, NJ 07866-0912. All rights reserved under the U.S.A., International, and Pan-American Copyright Conventions. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, mechanical, photocopying, electronic recording or otherwise, without the prior written permission of the publisher. Opinions expressed in articles are those of the authors and do not necessarily reflect those of Advantage Business Media LLC or the Editorial Board.

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There are two sides to every story.

But with Contec’s DualClean™ Softwall Strip Cleaner, there is only one ending - happily ever after.

Clean both sides of a softwall strip at the same time!

• Effectively and efficiently cleans both sides of a curtain strip in a single pass.

• Perfect for 4” - 12” (10 - 30cm) curtain strips.

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• Electropolished frame is resistant to most chemicals and disinfectants and can be sterilized.

• Tension on the curtain strip is easily controlled.

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To make your softwall cleaning and disinfecting more effective and efficient, choose DualClean from Contec. Learn more by visiting our web site: www.contecinc.com.

Best Cleanroom Consumables Product